PROJECT SUMMARY/ABSTRACT Alcohol dependence is a chronic relapsing disease with adverse consequences that extend well beyond the period of drinking and represents an important public health problem. Cost-effectiveness analyses (CEAs) that fully account for the impact of alcohol dependence treatment on short- and long-term alcohol-related consequences can help expand the delivery of cost-effective alcohol treatments and provide more accurate information to decision makers on which treatments represent a better use of scarce resources. However, clinical studies may not capture long-term consequences because they usually do not follow patients for their lifetime; therefore, a lifetime perspective can be achieved more easily through the use of mathematical models, such as state-transition models. The few previous CEAs that used modeling focused mainly on abstinence-based outcomes disregarding patterns of consumption (e.g., binge drinking episodes); assumed that the outcomes of clinical trials remained the same over a patient's lifetime; and did not attempt to model relapse, multiple treatment episodes, and natural recovery. This study will address these gaps and present a significant contribution by developing the first dynamic model that incorporates long-term drinking patterns and associated consequences in the CEA of alcohol treatments in the United States. We will extend a previous model developed by Dr. Carolina Barbosa and colleagues and will apply it to identify the most cost- effective, evidence-based alcohol dependence treatment from the U.S.-based Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study, the largest randomized, placebo- controlled trial of alcohol treatments in the United States. Our study will provide new lifetime estimates from COMBINE, including long-term drinking outcomes, life expectancy, quality of life, productivity, and alcohol- related costs, and allow the economic value of alcohol treatments to be compared to other medical services. We will also investigate the impact of future treatment episodes and avoid the simplistic assumption applied in clinical trials that treatment is a one-off time-constrained intervention, therefore, explicitly acknowledging the chronic nature of alcohol dependence. Specifically, the proposed study has the following two aims: (1) develop a lifetime dynamic model that accounts for the short- and long-term impact of alcohol drinking patterns to achieve better estimates of alcohol treatment effectiveness and cost-effectiveness; and (2) use the model to estimate the long-term costs and outcomes of COMBINE treatments, under alternative future alcohol treatment scenarios, and the impact of COMBINE therapies by age, gender, and race/ ethnicity, producing long-term cost-effectiveness estimates for different subgroups. Our approach can be used in the comparative cost-effectiveness of other studies of alcohol treatment. This study will contribute to alcohol treatment research and influence current policy debates about the value of alcohol treatment.